Recently we have defined a unique role for metal ions as regulators of the enzymes of heme biosynthesis and degradation and have described a distinct heme b oxygenase enzyme whose production is increased by metal ions. We have observed that treatment of animals with metals causes a depression in the heart and kidney mitochondrial content of cytochromes possessing hemes a, b and c. We have also observed decreases in the heart content of mitochondrial cytochromes in a disease which causes increased heme degradation and the release of iron. Although these decreases were not related to the elevated heme oxygenase activity, it can be postulated that the activity of the enzymes of mitochondrial heme metabolism are also regulated by metal ions. Various metal ions accumulate in the body, and there is substantial evidence relating metal ion toxicity to their effects on the metabolic functions of the heart and kidney. For example, excessive mortality due to heart failure observed in individuals who are occupationally exposed to metal ions is linked to these agents. The proposed studies will encompass the regulatory action of metal ions on the metabolism of mitochondrial hemoproteins.